Chronic Acetylcholine high
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Hi everyone, for several weeks I have been experiencing symptoms of high acetylcholine as if the acetylcholinesterase enzyme was inhibited but not reversibly because otherwise the situation would return to normal in 2-3 days. Is there something that can be done to "unblock" this enzyme and promote the regular metabolism of acetylcholine? thank you all happy to be here too.
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Nothing ?
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@Highserotonin said in Chronic Acetylcholine high:
Hi everyone, for several weeks I have been experiencing symptoms of high acetylcholine as if the acetylcholinesterase enzyme was inhibited but not reversibly because otherwise the situation would return to normal in 2-3 days. Is there something that can be done to "unblock" this enzyme and promote the regular metabolism of acetylcholine? thank you all happy to be here too.
Although thiamine is known mainly for the production of acetylcholine, it is also believed to play a part in the production of acetylchonlinesterase. So I think it's possible that thiamine "modulates" the level of acetylcholine.
"Thiamine (vitamin B1), cofactor for various multi-enzyme complexes in energy metabolism, and plays a major role in the synthesis of cholinesterases such as acetylcholinesterase (AChE); butyrylcholinesterase (BChE). Present study deals with the changes in the cholinesterases, γ-aminobutyric acid (GABA) and serotonin in mice brain following thiamine deficiency. Experimental mice (6–8 week old) were made thiamine deficient by intraperitoneal injection of pyrithiamine hydrobromide and fed with thiamine-deficient diet. Animals were divided into three groups, Group I (Control), Group II (thiamine deficient mice for 8 days), and Group III (thiamine deficient mice for 10 days). The higher serotonin level whereas significant decreases in the AChE, BChE and GABA level were recorded in treated groups as compared to control. Hence, vitamin B1 deficiency disturbs the cholinergic system and neurotransmitters levels in brain which may lead to neurodegenerative diseases."
also:
"Hypothyroidism causes learning and memory impairment. Considering the neuroprotective properties of thiamine (Vitamin B1), this study was conducted to investigate the effects of thiamine on acetylcholinesterase (AChE) activity, oxidative damage, and memory deficits in hypothyroid rats.In this study, 50 rats (21 days old) were randomly divided into 5 groups and treated with propylthiouracil (0.05% in drinking water) and thiamine (50, 100, and 200 mg/kg, oral) for 7 weeks. Following that, Morris water maze (MWM) and passive avoidance (PA) tests were performed. Finally, oxidative stress indicators and AChE activity were measured in brain tissue.Treatment of hypothyroid rats with thiamine, especially at 100 and 200 mg/kg, alleviated the ability to remember the location of the platform as reflected by less time spent and distance to reach the platform, during the MWM test (P < 0.05 to P < 0.001). In the PA test, the latency to enter the dark chamber and light stay time were increased in rats who received thiamine compared to the hypothyroid group (P < 0.05 to P < 0.001). In addition, thiamine increased the levels of total thiol groups and superoxide dismutase while decreasing the levels of malondialdehyde and AChE.Our results suggest that thiamine supplementation could effectively improve memory loss in a rat model of hypothyroidism. The positive effects of thiamin on the learning and memory of hypothyroid rats may be due to amelioration of redox hemostasis and cholinergic disturbance."
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@mostlylurking
Thank you so does B1 not necessarily increase choline or rather does it increase final degradation if acetylcholinesterase rises?
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Either by upregulating the enzyme using Forskolin or Tyrosine, using a D2 partial agonist, or an NMDA antagonist like memantine, or all three at the same time.
Take a look at this article by Hans : https://testonation.com/2020/06/26/the-high-acetylcholine-syndrome/
I've struggled with this problem for a long time and it made me intolerant to Thiamine even if my body needed it as it was the only supplement that was improving my energy and breathing but was giving me severe anxiety.
I even had a post on the RPF where I tried a lot of different things from Benadryl, Scopolamine, Forskolin, I couldn't update it because I didn't have the right anymore to post in the forum.
Anti-cholinergics like Cyproheptadine, Diphenhydramine or Scopolamine are great at improving symptoms short term, Forskolin is better for mid-term, but in the long run, you got to fix the acetylcholine system, it's not a problem of high or low acetylcholine, it's mainly why the body doesn't use it properly.
Thiamine will improve your acetylcholine status but only temporary, a combination of Thiamine and an NMDA antagonist like magnesium L-Threonate, memantine or agmatine will fix it long term. At least, it's what it did for me after trying hundreds of supplements and medications.
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The acetylcholinesterase enzyme is tightly regulated, so I wouldn't expect a problem be associated with that unless you're taking something that inhibits it.
Is your serotonin and adrenaline high too? A lot of times acetylcholine, serotonin, and adrenaline will all be elevated together if someone is overmethylating. In which case, glycine or niacinamide can be a useful treatment course.
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@Highserotonin said in Chronic Acetylcholine high:
@mostlylurking
Thank you so does B1 not necessarily increase choline or rather does it increase final degradation if acetylcholinesterase rises?
It's a complicated subject. Thiamine (B1) seems to "modulate" the level of acetylcholine. In other words, it raises the level , but it also involved in acetylcholinesterase which lowers the level of acetylcholine. It facilitates the proper functioning of the system.
Searching for "thiamine" and "acetylcholine" and also searching for "thiamine" and "acetylcholinesterase" may yield more information. (do use the quotation marks in your search.)
I suspect if you have a good supply of choline but are deficient in B1 your body will not be able to make acetylcholine.
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@Mulloch94 Hi, I did serum tests and cholinesterase is in the low threshold. I should have the erythrocyte test on Monday. There is something that is non-reversibly blocking the enzyme
️. In the meantime, I no longer know how to manage the symptoms. It's hellish because I've already had chronic degenerative processes for many years. At home I have magnesium bisglycinate with P5P, magnesium Epson (sulfate). Can they help as you kindly indicated? NAC seemed to help increase acetylcholinesterase activity but now after a few days it stopped working, as did lipoic acid. -
@Appa Thanks, it sounds like there's something inhibiting it. the hospital didn't give any importance but if the symptoms continue I will have to return in the meantime I have also tried chelators such as zeolite, NAC and alpha lipoic acid but I suspect something highly selective is needed
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@Appa I would keep away from Mg-L-Thr
https://assets.cureus.com/uploads/original_article/pdf/201718/20231207-19443-1lqkua0.pdf
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@Highserotonin Sorry you're going through some shit right now. I think the best thing to do would be approach it from a multi-faceted angle. It's probably something I'd try if I had really high acetylcholine without knowing the exact cause. First thing to do is antagonize the receptors with diphenhydramine. Dosage might be a bit finicky. You'll need to find that perfect balance between what gives symptom relief and what makes you too drowsy. But generally 25-50mgs would be a good starting dose. You could also stack that with something like Forskolin, which has been shown to upregulate acetylcholinesterase (R). I've only seen in-vitro stuff thus far, so not sure what dosage would be best. But a quality and clean product would probably work. Barlowe's Herbals make great botanicals, including forskolin. Whatever their recommended dosage is will suffice. The final thing I would do is attempt to put the breaks on choline's synthesis de novo. This can be done by dramatically lowering your methionine intake in an attempt to slow down SAM (S-adenosylmethionine) acitivty which is needed to donate methyl groups for choline synthesis.
To recap, where going to directly antagonize the receptors with Benadryl, hopefully upregulate it's breakdown with Forskolin, and slow down the synthesis of the main precursor with methionine restriction.
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@Highserotonin What symptoms are you even experiencing?
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@Yenn Diarrhea alternating with constipation, sensation of not breathing even if saturation remains normal, insomnia, vivid dreams when I fall asleep, alertness, asthenia, decreased muscle tone, confusione, all of which would correspond to a cholinergic crisis induced by acetylcholinesterase blockade
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@Highserotonin What does your diet look like?
Some individuals are more sensitive to the solanaceous glycoalkaloids in nightshades (e.g. due to BChE deficiencies). Of course there is also the problem of non-organic food and pesticides which act as cholinesterase inhibitors.
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@Korven Hi, it's the usual diet with the usual foods except vegetable oils and dried fruit. I've never had a problem with eggs and nightshades. The most serious problem is not being credible in two hospitals because they are based on the muscle biopsy I did and therefore interpret the symptoms only as general worsening (even the neurologist). Quite frustrating because they are typical symptoms of cholinergic syndrome/intoxication (from an external agent). Add to that the fact that I already have a weakened brain and muscles, we say putting fuel on the fire.
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@Mulloch94 Perhaps you miss a fundamental step that by the time the substance leaves the system the final acetylcholine will perhaps be higher than before. Do you understand what I mean? a typical example is when you use Cypro for example you might feel terrible during it but when it comes out you will feel better due to a matter of receptor under-regulation and over-regulation. I gave a random example but it could apply to anything we introduce. I absolutely need to reactivate acetylcholinesterase or antagonize whatever is blocking the enzyme. They mention atropine scopolamine but the hospital should do it, not me!